Title: Understanding Non-covalent Interaction in Carbon Nanotube/Anticancer Drug Conjugates with the First-principles Based Theoretical Methods Carbon nanomaterials have shown great potential in biomedical applications, such as carbon nanotube (CNT)-based targeting drug delivery system (DDS) for cancer chemotherapy. A typical CNT targeting DDS system consists of functional groups that enhance solubility and biocompatibility of the CNT system, anticancer drugs with strategically designed module regulating drugs loading extracellularly and releasing inside tumor cells and tumor-targeting module recognizing tumor cells. Non-covalent interactions widely exist in the DDS conjugates, and play very important roles in every essential step, including functionalization of CNTs, loading and releasing of anticancer drugs, cellular internalization of the DDS as well as escaping of the CNT after function of the DDS. However, such weak interactions in the CNT DDS conjugates are far from being well understood at a molecular level. Major goal of the project is therefore to gain a deep understanding of the non-covalent interactions between anticancer drug and functionalized SWCNT in the DDS through state-of-the-art theoretical tools, such as quantum mechanical (QM), classical molecular dynamics (MD), and QM/MM. Such knowledge could eventually help design a new generation of drug delivery systems based on CNTs. The research objectives are: 1) To provide a good understanding about the non-covalent interactions for the CNT- based DDS for a couple of effective typical anticancer drugs (doxorubicin and paclitaxel) via multiscale molecular modeling and simulations, specifically, the effects of various functionalization of CNT on the drug loading/releasing mechanism, their dependences on pH, length, dimeter and chirality of CNT, and degree and type of functionalization of the CNTs. Eventually, develop an ab initio derived guideline for regulating the design of CNT-based DDS. 2) To clarify a few important issues for the design of the CNT-based DDS by analyzing the above extensive multiscale theoretical investigation, such as driving forces that lead to the different loading mechanisms for the DOX and PTX, the optimum degree of functionalization of CNT that is necessary and sufficient for drug loading, and the favorable drug loading mechanism (adsorption on sidewall of f-SWCNT against encapsulation). 3) To investigate the adsorptions of the anticancer drugs on a few novel carbon nanomaterials such as hydrophilic carbon clusters (HCC), and defective graphenes. The results can be used to test the hypothesis that the functionalized N/O/B-doped graphenes may be potential candidates for drug carrier.